Cutaneous T cell lymphoma (CTCL) is a maiignancy of CD4 helper T cells which appears first in the skin then slowly progresses to blood, lymph nodes and visceral organs. This group of diseases includes the leukemic erythroderma known as Sezary syrdrome and the nonleukemic disease known as mycosis fungoides. The neoplastic T cells infiltrating skin, lymph nodes and blood are atypical large lymphocytes with a serpentine or cerebriform nucleus which express T cell activation markers and appear to be clonal in origin. Despite serveral efforts, no one has been successful in growing HTLVI-negative CTCL cells from blood or skin of patients presumably due to functional defects in their activation or clonal expansion. We have been successful in growing, from the blood of 13 out of 15 Sezary syrdrome patients, long-term T cell lines and clones which have the phenotyic, karyotypic, or clonotypic characteristics of neoplastic, non- HTLVI, Sezary cell. We propose to define the signals required for their activation and growth by: one, characterizing a potentially novel lymphokine (here called SAF) required for the induction of functional interleukin 2 receptors (IL2R) on Sezary cells; two, examining the role of accessory cells in the responsiveness Sezary cells to SAF and IL2; three, identifying receptors for SAF on Sezary cells at different stages of activation; four, examining human skin keratinocytes for the expression of SAF and IL2 required for Sezary cell activation and proliferation. These studies may result in a definition of the growth regulatory signals for these neoplastic T cells which may suggest new concepts of intervention in the progression of this disease.